title: RIG-I-like receptors mediate innate antiviral response in mouse testis.
abstract: The testis is an immune privileged organ in which the tissue-specific cells have adopted effective innate immune functions against microbial pathogens. Toll-like receptors (TLRs) mediate innate immune response in the testis. The current study demonstrates that melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) initiate the testicular innate antiviral response. Both MDA5 and RIG-I are expressed in Leydig cells, and MDA5 is also expressed in spermatids. Polyinosinic-polycytidylic acid [poly(I:C)], a common agonist of MDA5 and RIG-I, significantly induces the expression of type I interferons (IFN-α/β) and antiviral proteins, including IFN-stimulated gene 15, 2'5'-oligoadenylate synthetase 1, and Mx GTPase 1, in primary TLR3-deficient (TLR3(-/-)) Leydig and germ cells. Moreover, major proinflammatory cytokines, including TNF-α and IL-6, are significantly up-regulated by poly(I:C) in these testicular cells. The poly(I:C)-induced innate antiviral response in the testicular cells is significantly reduced by knockdown of individual MDA5 and RIG-I using specific small interfering RNA. We also provide evidence that local injection of poly(I:C) induces antiviral response in the testis of TLR3(-/-) mice. These data provide novel insights into the mechanisms underlying testicular antiviral response.
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005 China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Yu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000276:immunology* / Q000821:virology*
chemical_list: D016207:Cytokines; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C